An age-of-allele test of neutrality for transposable element insertions

TL;DR

This paper introduces a new neutrality test for transposable element insertions that accounts for non-constant transposition rates and uses insertion age to better understand TE dynamics and selection in populations.

Contribution

It develops a novel age-of-allele based model for TE insertions that relaxes the constant transposition rate assumption and incorporates demographic effects.

Findings

Explains 80% of variance in TE allele frequencies using age alone.

Provides evidence for negative selection on most TEs.

Detects positive selection on a small subset of TEs.

Abstract

How natural selection acts to limit the proliferation of transposable elements (TEs) in genomes has been of interest to evolutionary biologists for many years. To describe TE dynamics in populations, many previous studies have used models of transposition-selection equilibrium that rely on the assumption of a constant rate of transposition. However, since TE invasions are known to happen in bursts through time, this assumption may not be reasonable in natural populations. Here we propose a test of neutrality for TE insertions that does not rely on the assumption of a constant transposition rate. We consider the case of TE insertions that have been ascertained from a single haploid reference genome sequence and have subsequently had their allele frequency estimated in a population sample. By conditioning on the age of an individual TE insertion (using information contained in the number of substitutions that have occurred within the TE sequence since insertion), we determine the probability distribution for the insertion allele frequency in a population sample under neutrality. Taking models of varying population size into account, we then evaluate predictions of our model against allele frequency data from 190 retrotransposon insertions sampled from North American and African populations of Drosophila melanogaster. Using this non-equilibrium model, we are able to explain about 80% of the variance in TE insertion allele frequencies based on age alone. Controlling both for nonequilibrium dynamics of transposition and host demography, we provide evidence for negative selection acting against most TEs as well as for positive selection acting on a small subset of TEs. Our work establishes a new framework for the analysis of the evolutionary forces governing large insertion mutations like TEs, gene duplications or other copy number variants.